ClinVar Miner

Submissions for variant NM_024675.4(PALB2):c.1348A>C (p.Asn450His)

gnomAD frequency: 0.00001  dbSNP: rs62625274
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 8
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000212791 SCV000149976 uncertain significance not provided 2024-09-15 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis indicates that this missense variant does not alter protein structure/function; Observed in co-occurrence with a second missense variant in PALB2 in an individual undergoing genetic testing for hereditary breast and ovarian cancer; however, it is unknown whether the variants were on the same or opposite chromosomes (in cis or trans) (PMID: 38136308); This variant is associated with the following publications: (PMID: 38136308)
Ambry Genetics RCV000116067 SCV000216351 uncertain significance Hereditary cancer-predisposing syndrome 2023-08-02 criteria provided, single submitter clinical testing The p.N450H variant (also known as c.1348A>C), located in coding exon 4 of the PALB2 gene, results from an A to C substitution at nucleotide position 1348. The asparagine at codon 450 is replaced by histidine, an amino acid with similar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV000198442 SCV000255077 uncertain significance Familial cancer of breast 2023-09-21 criteria provided, single submitter clinical testing Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt PALB2 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. ClinVar contains an entry for this variant (Variation ID: 128119). This sequence change replaces asparagine, which is neutral and polar, with histidine, which is basic and polar, at codon 450 of the PALB2 protein (p.Asn450His). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with PALB2-related conditions.
Color Diagnostics, LLC DBA Color Health RCV000116067 SCV000685875 uncertain significance Hereditary cancer-predisposing syndrome 2023-09-19 criteria provided, single submitter clinical testing This missense variant replaces asparagine with histidine at codon 450 in the PALB2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with PALB2-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Counsyl RCV000198442 SCV000785652 uncertain significance Familial cancer of breast 2017-10-19 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000765274 SCV000896527 uncertain significance Familial cancer of breast; Fanconi anemia complementation group N; Pancreatic cancer, susceptibility to, 3 2021-11-30 criteria provided, single submitter clinical testing
Myriad Genetics, Inc. RCV000198442 SCV004019657 uncertain significance Familial cancer of breast 2023-03-31 criteria provided, single submitter clinical testing This variant is classified as a variant of uncertain significance as there is insufficient evidence to determine its impact on protein function and/or cancer risk.
Baylor Genetics RCV000198442 SCV004202167 uncertain significance Familial cancer of breast 2023-12-18 criteria provided, single submitter clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.